The present invention relates to the field of biological decontamination. The invention finds particular application in connection with the removal and/or destruction of harmful biological materials, such as prions (proteinaceous-infectious agents), from medical, dental, and pharmaceutical instruments and will be described with particular reference thereto. It will be appreciated, however, that the method and system of the present invention may be utilized in biological decontamination of a wide range of equipment, instruments, and other surfaces contaminated with prion infected material, such as pharmaceutical preparation facilities, food processing facilities, laboratory animal research facilities including floors, work surfaces, equipment, cages, fermentation tanks, fluid lines, and the like.
The term “Prion” is used to describe proteinaceous-infectious agents that cause relatively similar brain diseases in humans and/or in animals, which are invariably fatal. These diseases are generally referred to as transmissible spongiform encephalopathies (TSEs). TSEs include Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD) in humans, Bovine Spongiform Encephalopathy (BSE) in cattle, also know as “Mad Cow Disease,” Scrapie in sheep, and Wasting Disease in elk. All of these diseases attack the neurological organs of the animal or animals which are susceptible to the particular disease. They are characterized by initially long incubation times followed by a short period of neurological symptoms, including dementia and loss of coordination, and eventually death.
The infectious agent responsible for these diseases is thought to be a simple protein, with no associated nucleic acids. The pathogenic mechanism for such prion diseases is proposed to involve an initially normal host encoded protein. The protein undergoes a conformational change to an abnormal form (a prion), which has the ability of self-propagation. The exact cause of this change is, at present, unknown. The abnormal form of the protein is not broken down effectively in the body and its accumulation in certain tissues (in particular neural tissue) eventually causes tissue damage, such as cell death. Once significant neural tissue damage has occurred, the clinical signs are observed.
Prion diseases may thus be classified as protein aggregation diseases, which also include several other fatal diseases, such as Alzheimer's disease and amyloidosis. In the case of CJD, the most prevalent prion disease in humans (occurring in roughly 1:1,000,000 of the population), about 85% of cases are thought to arise sporadically, about 10% are thought to be inherited, and about 5% arise iatrogenically.
Although not considered to be highly contagious, prion diseases can be transmitted by certain high-risk tissues, including the brain, spinal cord, cerebral spinal fluids, and the eye. Iatrogenic transmission has been reported during several procedures, including dura-mater grafting, corneal transplants, pericardial homografts, and through human gonadotropin and human growth hormone contamination. Transmission via medical devices has also been reported, including from neurosurgical instruments, depth electrodes, and other devices used for surgical procedures in close proximity to the central nervous system. Concerns are being raised that procedures previously considered to be “low risk” in terms of prion infection, such as tonsillectomy and dental procedures, may pose unacceptable risks of infection, particularly, if the incidence of prion-related diseases increases.
After a surgical procedure on a prion infected patient, prion containing residue may remain on the surgical instruments, particularly neurosurgical and opthalmological instruments. During the long incubation period, it is extremely difficult to determine whether a surgical candidate is a prion carrier.
Different levels of microbial decontamination are recognized in the art. For example, sanitizing connotes free from dirt or germs by cleaning. Disinfecting calls for cleansing in order to destroy harmful microorganisms. Sterilization, the highest level of biological contamination control, connotes the destruction of all living microorganisms.
It is now known that certain biological materials, which do not live or reproduce in the conventional sense, such as prions, are nevertheless capable of replication and/or transformation into harmful entities. We use herein the term “deactivation” to encompass the destruction of such harmful biological materials, such as prions, and/or their ability to replicate or undergo conformational changes to harmful species.
Prions are notoriously very hardy and demonstrate resistance to routine methods of decontamination and sterilization. Unlike microorganisms, prions have no DNA or RNA to destroy or disrupt. Prions, due to their hydrophobic nature, tend to aggregate together in insoluble clumps. Under many conditions that lead to successful sterilization of microorganisms, prions form tighter clumps, which protect themselves and underlying prions from the sterilization process.
The World Health Organization (1997) protocol for prion deactivation calls for soaking the instrument in concentrated sodium hydroxide or hypochlorite for two hours followed by one hour in an autoclave. These aggressive treatments are often incompatible with medical devices, particularly flexible endoscopes and other devices with plastic, brass, or aluminum parts. Many devices are damaged by exposure to high temperatures. Chemical treatments, such as strong alkali, are damaging to medical device materials or surfaces in general. Glutaraldehyde, formaldehyde, ethylene oxide, liquid hydrogen peroxide, most phenolics, alcohols, and processes such as dry heat, boiling, freezing, UV, ionizing, and microwave radiation have generally been reported to be ineffective. There is a clear need for products and processes that are effective against prions yet compatible with surfaces.
Ernst and Race (J. Virol. Methods 41:193-202 (1993)) describe a study in which a phenol-based disinfectant product (LpH™, obtainable from STERIS Corp., Mentor, Ohio), which according to the authors, contains p-tertiary-amylphenol, o-benzyl-p-chlorophenol, and 2-phenyl phenol, was found to be effective against scrapie. The study investigated the effects of concentration (0.9-90%) and exposure time (0.5-16 hrs) on the level of infection removed in scrapie-sensitive hamster models injected with hamster brain homogenate. Relatively high concentrations of LpH™ or extended periods were found to be effective in reducing the presence of the prion. In other studies, phenols have generally been found not to be effective against prions.
The present invention provides a new and improved method of treatment of surfaces contaminated with prion-infected material, which overcomes the above-referenced problems and others.